This is a K08 initial application for Dr. James Flory, an endocrinologist and young investigator pursuing patient-oriented comparative effectiveness research on the care of type 2 diabetes mellitus (T2DM). A K08 award will provide him with the means to acquire skills in three key career development areas: 1) clinical epidemiology, 2) qualitative research, and 3) clinical trial design. By acquiring these skills, Dr. Flory will fulfil his long-term career goal of becoming an independent clinical investigator. Dr. Flory has a primary mentor, Dr. Alvin Mushlin, who is a leading epidemiologist and internist with extensive experience mentoring K-grant awardees. He will also work with a co-mentor, Dr. Sean Hennessy, a leading pharmacoepidemiologist. In addition, Dr. Flory has two key collaborators: Dr. Joshua Richardson, an expert in the application of qualitative research to biomedical informatics, and Dr. David Brillon, an endocrinologist and clinical researcher specializing in diabetes. The motivating clinical problem for this proposal is the fact that although metformin is the first-line drug therapy for T2DM and confers unequalled long-term clinical benefits, it is under-utilized. In particular, 16% of patients discontinue metformin at 6 months and close to a third discontinue it at one year. Dr. Flory's central hypothesis is that much of this non-persistence (i.e., early discontinuation) is due to patient-centered factors specific to metformin and that better prescribing practices and prescriber-patient communication can enhance metformin persistence. To test this hypothesis and translate it into a pragmatic intervention, Dr. Flory proposes to collect epidemiologic and qualitative data on metformin non-persistence and then design and pilot an intervention in a small pragmatic clinical trial. These activities will la the groundwork for a large-scale pragmatic randomized trial to be proposed in an R01 application during the K08 award period. Aim 1 will test the hypothesis that metformin non-persistence is common and leads to observably worse short-term clinical outcomes. Aim 2 will test the hypothesis that non-persistent patients and their providers will offer potentially modifiable reasons for metformin non-persistence. Aim 3 will test the hypothesis that a pragmatic clinical trial of a patient-centered intervention to reintroduce metformin to previously non-persistent patients is feasible and likely to result in increased appropriate use of metformin to treat T2DM. The proposed research is significant because positive results will lead to identification of an intervention to allow more patients to benefit from metformin. Negative results would provide information on the nature of metformin non-persistence and lay groundwork for alternative approaches to optimizing care of these patients.